Induction of Tumors in Mice Given a Minute Single Dose of Dibenz[a,h]anthracene or 3-Methylcholanthrene as Newborns. A Dose-Response Study

Abstract

Newborn, noninbred albino mice were given a single subcutaneous injection of either dibenz[a,h]anthracene (DBA) or 3-methyl-cholanthrene (MCA) in olive oil. The males were killed at 54 to 55 weeks of age, the females at 78 to 79 weeks. Eight logarithmically spaced dose levels of each carcinogen were used, ranging downward from 6.7 to 0.0031 μg of DBA and from 11.1 to 0.0051 μg of MCA. Control mice were given olive oil only. One hundred thirty litters were randomly distributed among the treatment and control groups. Subcutaneous fibrosarcomas at the site of the injection were induced at all dose levels of DBA, except one of the intermediate doses. In the animals given MCA, fibrosarcomas were induced at the 4 highest dose levels (11.1–0.4 μg) but not at the 4 lowest dose levels (0.137–0.0051 μg). Nearly all the subcutaneous fibrosarcomas appeared within the first 48 weeks after administration of carcinogen, and only one animal developed a fibrosarcoma after 56 weeks. At the highest DBA level (6.7 μg) and the two highest MCA levels (11.1 and 3.7 μg), the number of pulmonary tumors increased in animals autopsied during the first 55 weeks over those in control animals. Lung tumors were seen as early as 16 weeks after injection of the carcinogen. In female mice autopsied after 55 weeks, there was an increase in pulmonary tumors over controls at the 4 highest dose levels of both carcinogens, that is, from 0.2 μg upward for DBA and from 0.4 μg upward for MCA. A variety of other neoplasms, including leukemias, lymphomas, hepatomas, hemangiomas, and uterine tumors, were found in 10 to 13 percent of female mice 56 to 79 weeks old at death and in 0.8 to 4.5 percent of male mice 54 to 55 weeks old at death. These neoplasms did not appear to be related to the dose of carcinogen and were observed in controls as well as in mice given carcinogen.